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Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
MedLine Citation:
PMID:  22200086     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis, cytopenias, and a risk of transformation to acute myeloid leukemia (AML). However, only approximately 50% of primary MDS patients show clonal cytogenetic aberrations. To determine whether high-resolution microarray analysis would reveal new or additional aberrations, we analyzed 35 samples derived from patients with a diagnosis or suspicion of MDS and abnormal karyotypes. We used a whole-genome oligonucleotide microarray with targeted coverage of approximately 1900 genes associated with hematologic and other cancers. Clinically relevant copy number aberrations (CNAs) were identified by microarray-based comparative genomic hybridization (aCGH) in all samples (range 1-31, median 5). In 28 of 35 samples (80%), aCGH revealed new cytogenetic aberrations not seen by karyotype or fluorescence in situ hybridization (FISH). Furthermore, 132 cryptic aberrations (≤5 Mb) were identified in 25 cases (71.4%) including deletions of NF1, RUNX1, RASSF1, CCND1, TET2, DNMT3A, HRAS, PDGFRA and FIP1L1. Additionally, aCGH clarified known complex aberrations in 17 of 35 samples (48.6%). Finally, our results using whole-genome arrays with higher density coverage targeted to cancer features demonstrate the usefulness of arrays to identify rare and cryptic recurring imbalances that may prove to be significant in disease progression or transformation to AML and may improve the suitability or efficacy of molecularly targeted therapy.
Authors:
Kathryn A Kolquist; Roger A Schultz; Aubry Furrow; Theresa C Brown; Jin-Yeong Han; Lynda J Campbell; Meaghan Wall; Marilyn L Slovak; Lisa G Shaffer; Blake C Ballif
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer genetics     Volume:  204     ISSN:  2210-7762     ISO Abbreviation:  Cancer Genet     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-12-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101539150     Medline TA:  Cancer Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  603-28     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Sacred Heart Medical Center, Spokane, WA, USA.
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